Oseltamivir Group Research Articles

Real-world effectiveness and safety of Baloxavir Marboxil or Oseltamivir in outpatients with uncomplicated influenza A: an ambispective, observational, multi-center study.

Baloxavir Marboxil is a per oral small-molecule antiviral for the treatment of influenza. While the efficacy and safety of Baloxavir Marboxil have been thoroughly characterized across an extensive clinical trial, studies on the effectiveness of Baloxavir Marboxil in a real-world setting are still scarce. We conducted an ambispective, observational, multi-center study that enrolled uncomplicated in-fluenza outpatients treated with Baloxavir Marboxil or Oseltamivir in East China. The primary endpoint was time from treatment to alleviation of all influenza symptoms (TTAIS). The secondary endpoints included time from treatment to alleviation of fever (TTAF) and household transmission during the duration of influenza. A total of 509 patients were enrolled. The median TTAIS in the Baloxavir Marboxil group and the Oseltamivir group was 28.0 h (IQR, 20.0 to 50.0) and 48.0 h (IQR, 30.0 to 67.0), respectively. The median TTAF in the Baloxavir Marboxil group and the Oseltamivir group was 18 h (IQR, 10.0-24.0) and 30.0 h (IQR, 19.0-48.0). In the COX multivariable analysis, Baloxavir Marboxil reduced the duration of influenza symptoms (HR = 1.36 [95%CI:1.12-1.64], p = 0.002) and the duration of fever (HR = 1.93 [95%CI:1.48-2.52], p < 0.001) compared to Oseltamivir. When antiviral drugs were given within 12-48 h after symptom onset, the Baloxavir Marboxil group had a significantly shorter TTAIS compared to the Oseltamivir group. There was no significant difference in the rate of adverse events between the two group (p = 0.555). Baloxavir Marboxil was superior to Oseltamivir in alleviating influenza symptoms in outpatients with uncomplicated influenza. Our findings suggested that compared to Oseltamivir, Baloxavir Marboxil might be more appropriate for patients with influenza 12- 48 h after symptom onset.

Clinical outcomes of baloxavir versus oseltamivir in immunocompromised patients.

Neuraminidase inhibitors, including oseltamivir, are the treatment standard for influenza. Baloxavir, a novel antiviral, demonstrated comparable outcomes to oseltamivir in outpatients with influenza. Baloxavir was equally effective as oseltamivir in a retrospective study of hospitalized patients with influenza at our institution. However, the efficacy of baloxavir in immunocompromised patients is unclear. We conducted a retrospective cohort study of immunocompromised adult patients hospitalized with influenza A who received baloxavir from January 2019 to April 2019 or oseltamivir from January 2018 to April 2018. Demographic and clinical outcomes were assessed. Primary outcomes were time from antiviral initiation to resolution of hypoxia and fever. Secondary outcomes were length of stay (LOS), intensive care unit (ICU) care, ICU LOS, and 30-day mortality. Of 95 total patients, 52 received baloxavir and 43 received oseltamivir. Other than younger age (57.5vs. 65; p = .035) and longer duration between vaccination and symptom onset (114vs. 86 days; p = .001) in the baloxavir group, baseline characteristics did not differ. H1 was the predominant subtype in the baloxavir group (65.3%) versus H3 in the oseltamivir group (85.7%). When comparing baloxavir to oseltamivir, there was no significant difference in median time from antiviral initiation to resolution of hypoxia (59.9vs. 42.5 h) and to resolution of fever (21.6vs. 26.6 h). There were no differences in secondary outcomes. Baloxavir was not associated with longer time to resolution of hypoxia or fever in comparison to oseltamivir. Results must be taken in context of variations in seasonal influenza subtype and resistance rates.

Safety and effectiveness of baloxavir marboxil and oseltamivir for influenza in children: a real-world retrospective study in China.

To evaluate the safety and effectiveness of baloxavir marboxil (baloxavir) and oseltamivir in pediatric influenza patients in China. Patients filling a prescription for baloxavir or oseltamivir within 48 h following an influenza-related outpatient visit were identified in Children's Hospital of Fudan University in China between March 2023 and December 2023. Outcomes were assessed after antiviral treatment and included the incidence of adverse reactions and the duration of fever and other flu symptoms. A total of 1430 patients infected with influenza A were collected and 865 patients (baloxavir: n = 420; oseltamivir: n = 445) finally included. The incidence of adverse reactions of nausea and vomiting was significantly different between the baloxavir group (2.38%) and the oseltamivir group (12.13%) [P < 0.001, OR = 4.2526, 95%CI (2.0549, 9.6080)]. No differences in other adverse reactions were observed between the two groups. The mean duration of fever in baloxavir group (1.43d) was significantly shorter than that in oseltamivir group (2.31d) [P < 0.001, 95%CI (0.7815, 0.9917)]. There were no differences in the mean duration of nasal congestion and runny nose, sore throat, cough, and muscle soreness between two groups. The incidence of nausea and vomiting is lower with baloxavir compared to oseltamivir, and the duration for complete fever reduction is shorter with baloxavir than with oseltamivir. The results indicate that baloxavir is well tolerated and effective in Chinese children.

Combination therapy of nitazoxanide with oseltamivir compared with oseltamivir in hospitalized patients with seasonal influenza.

Antiviral combinations have been proposed as treatment for influenza in order to increase the antiviral activity by action at different sites of action as well as obviate the emergence of drug resistance to the commonly used antiviral agents like oseltamivir. Nitazoxanide has been found to exhibit anti-influenza viral activity with clinical benefit in a previous study. We recruited 242 cases of SARI, among whon 67 were confirmed to have influenza viral infection. In a randomized blinded fashion, 34 patients received a combination of nitazoxanide and oseltamivir whereas 33 cases received oseltamivir alone. Clinical parameters were followed in both groups and the nasal swabs were re-tested on day 6 for influenza positivity and the cycle threshold (CT) values. No significant differences were observed in terms of time for resolution of fever, other symptoms, and SOFA scores. Nine patients succumbed during the course of the illness that included three in the oseltamivir group and six in the combination group. All but one of those who expired had an underlying co-morbid illness. Our preliminary data suggest that the addition of nitazoxanide does not improve outcomes in hospitalized patients with influenza. Larger studies are recommended for statistically robust conclusions.

Early Fever Resolution in Early Childhood Influenza Treated with Baloxavir Marboxil: A Retrospective Study Compared to Those with Oseltamivir.

Background and Objectives: Baloxavir marboxil is a novel cap-dependent endonuclease inhibitor prescribed for influenza treatment. Unlike neuraminidase inhibitors like oseltamivir, which impair viral release from infected host cells, baloxavir blocks influenza virus proliferation by inhibiting viral mRNA transcription. This study aimed to compare the effectiveness of baloxavir and oseltamivir for the treatment of early childhood influenza. Materials and Methods: Of 1410 patients diagnosed with influenza between 2015 and 2018 at a Japanese primary care outpatient clinic, 1111 pediatric patients aged 0-6 years who were treated with baloxavir (n = 555) or oseltamivir (n = 556) were enrolled retrospectively. The following clinical factors were compared between patients treated with baloxavir and oseltamivir: age, sex, time from fever onset to drug administration (<24 h or 24-48 h), time from drug administration to fever reduction, influenza type (A or B), and influenza vaccination before disease onset. The duration of the fever, which was used as an index of clinical effectiveness, was compared using the log-rank test. Clinical factors associated with fever duration were determined using multivariate logistic regression analysis. Results: Median age (3.0 vs. 2.5 years), influenza type A (99% vs. 47%), median duration from drug administration to fever resolution (1 day vs. 2 days), and influenza vaccination (done, 41% vs. not done, 65%) were significantly different between the baloxavir and oseltamivir groups (p < 0.001). The number of patients with a fever duration of one day was 553 (99.6%) in the baloxavir group and 6 (1.1%) in the oseltamivir group (p < 0.001). Baloxavir use was only significantly associated with fever duration in the multivariate analysis (odds ratio 50,201, p < 0.001). Apparent adverse effects were not observed in the baloxavir-treated group. Conclusions: Baloxavir treatment resulted in a shorter fever duration than oseltamivir treatment in early childhood influenza.

Systematic review and meta-analysis of the efficacy and safety of oseltamivir (Tamiflu) in the treatment of Coronavirus Disease 2019 (COVID-19).

Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.

Maxing Shigan Decoction improves lung and colon tissue damage caused by influenza virus infection through JAK1/2-STAT1 signaling pathway

Based on Janus kinase 1/2-signal transducer and activator of transcription 1(JAK1/2-STAT1) signaling pathway, this study explored the immune mechanism of Maxing Shigan Decoction in alleviating the lung tissue and colon tissue damage in mice infected with influenza virus. The influenza virus infection was induced in mice by nasal drip of influenza virus. The normal group, model group, oseltamivir group, antiviral granule group, and Maxing Shigan Decoction group were designed. After intragastric administration of corresponding drugs or normal saline for 3 or 7 days, the body mass was measured, and lung index, spleen index, and thymus index were calculated. Based on hematoxylin-eosin(HE) staining, the pathological changes of lung tissue and colon tissue were observed. Enzyme-linked immunosorbent assay(ELISA) was used to detect serum levels of inflammatory factors interleukin-8(IL-8) and interferon-γ(IFN-γ), Western blot and real-time quantitative polymerase chain reaction(RT-qPCR) to determine the protein and mRNA levels of JAK1, JAK2, STAT1, interferon regulatory factor 9(IRF9), and IFN-γ in lung tissue and colon tissue. The results showed that after 3 and 7 days of administration, the body mass, spleen index, and thymus index were lower(P&lt;0.05 or P&lt;0.01), and the lung index was higher(P&lt;0.01) in the model group than in the normal group. Moreover, the model group showed congestion, edema, and infiltration of a large number of lymphocytes and macrophages in the lung tissue, irregular structure of colon mucosa, ulceration and shedding of epithelial cells, and infiltration of a large number of inflammatory cells. The model group had higher levels of serum IFN-γ(P&lt;0.01), higher protein and mRNA expression of JAK1, JAK2, STAT1, IRF9, IFN-γ in lung tissue(P&lt;0.05 or P&lt;0.01), higher level of JAK2 protein in colon tissue(P&lt;0.01), and higher protein and mRNA levels of STAT1 and IRF9(P&lt;0.05 or P&lt;0.01) than the normal group. Compared with the model group, Maxing Shigan Decoction group had high body mass, spleen index, and thymus index(P&lt;0.05 or P&lt;0.01), low lung index(P&lt;0.05 or P&lt;0.01), and significant alleviation of pathological injury in lung and colon. Moreover, lower serum level of IFN-γ(P&lt;0.05 or P&lt;0.01), protein and mRNA levels of JAK1, JAK2, STAT1, IRF9, and IFN-γ in lung tissue(P&lt;0.05 or P&lt;0.01), JAK2 protein level in colon tissue(P&lt;0.01), and protein and mRNA levels of STAT1 and IRF9(P&lt;0.05 or P&lt;0.01) were observed in the Maxing Shigan Decoction group than in the model group. After 3 days of administration, the level of serum IL-8 in the model group was significantly higher than that in the normal group(P&lt;0.01), and the level in the Maxing Shigan Decoction group was significantly reduced(P&lt;0.01). In conclusion, Maxing Shigan Decoction can significantly up-regulate body mass, spleen index, and thymus index, down-regulate lung index, reduce the levels of IL-8 and IFN-γ, and down-regulate protein and mRNA levels of JAK1, JAK2, STAT1, IRF9, and IFN-γ in lung tissue and protein and mRNA levels of JAK2, STAT1, and IRF9 in colon tissue, and alleviate pathological damage of lung tissue and colon tissue. The mechanism is the likelihood that it inhibits the activation of JAK1/2-STAT1 signaling pathway to alleviate the damage to lung and colon tissue damage.

Reduning Injection protects flu-infected mice by inhibiting infiltration of inflammatory cells in lung and down-regulating cytokine storm

This study aimed to explore the protective effect of Reduning Injection(RDN) on mice infected by influenza virus A/PR/8(PR8) and its immune regulatory roles during viral infection. In in vivo experiments, female C57 BL/6 mice were randomly divided into phosphate buffered saline(PBS) group, PR8-infected group, oseltamivir treatment group(OSV) and RDN treatment group. After 2 h of PR8 infection, mice in the oseltamivir group were gavaged with oseltamivir 30 mg·kg~(-1), and those in the RDN treatment group were injected intraperitoneally with RDN 1.5 mL·kg~(-1)once per day for seven consecutive days. The body weight of mice in each group was recorded at the same time every morning for 16 consecutive days. The line chart of body weight change was created to analyze the protective effect of RDN on flu-infected mice. The relative mRNA expression of different cytokines(IL-6, TNF-α, MCP-1, IL-1β, MIP-2, IP-10 and IL-10) in lung samples of flu-infected mice was detected by PCR. Flow cytometry was utilized to analyze the composition of immune cells of mouse BALF samples on day 5 after infection. Mouse macrophage cell line RAW264.7 was planted and treated by different concentrations of RDN(150, 300, 600 μg·mL~(-1)) for 24 h or 48 h, and cell proliferation was detected by CCK-8 assay. RAW264.7 cells and mouse primary peritoneal macrophages were stimulated with synthetic single stranded RNA(R837), which elicited the inflammatory response by mimicking the infection of single-stranded RNA viruses. The expression of cytokines and chemokines in the supernatants of above culture system was detected by ELISA and qPCR. On days 4, 5, 6, 7 and 15 after infection, the body weight loss of mice in the RDN treatment group was alleviated compared with that of PR8-infected mice(P&lt;0.05). RDN treatment obviously reduced lung index and the production of IL-6, TNF-α, MCP-1 and MIP-2 in lung tissues of flu-infected mice(P&lt;0.05). The proportions of macrophages, neutrophils and T cells in mouse BALF samples were analyzed by flow cytometry, and compared with PR8-infected mice, RDN decreased the proportion of macrophages in BALF of flu-infected mice(P&lt;0.05), and the proportion of T cells was recovered dramatically(P&lt;0.001). In CCK-8 assay, the concentrations of RDN(150, 300, 600 μg·mL~(-1)) failed to cause cytotoxicity to RAW264.7 cells. In addition, RDN lowered the expression of inflammatory cytokines such as IL-6, TNF-α,MCP-1, IL-1β, RANTES, and IP-10 and even anti-inflammatory cytokine IL-10 in R837-induced macrophages. RDN reduced the infiltration of inflammatory macrophages and the production of excessive inflammatory cytokines, alleviated the body weight loss of flu-infected mice. What's more, RDN restored the depletion of T cells, which might prevent secondary infection and deteriorative progression of the disease. Taken together, RDN may inhibit cytokine production and therefore down-regulate cytokine storm during the infection of influenza virus.

Oseltamivir Treatment for Influenza During the Flu Season of 2018-2019: A Longitudinal Study.

BackgroundOseltamivir resistance in influenza virus (IFV) has been of widespread concern. An increase in the frequency of viruses with reduced inhibition was observed. Whether oseltamivir is effective is uncertain. We conducted this study to understand the real-world situation in northern China and the clinical efficacy for patients with IFV infection after the use of oseltamivir.MethodsThe longitudinal study was performed on influenza-like illness (ILI) cases in a tertiary general hospital in Beijing, China during the flu season of 2018–2019. All ILI cases (≥18 years) were recruited into the study. We analyzed the effect of the oseltamivir therapy on the number of clinic visits, hospitalization frequency, and the duration of fever and cough.ResultsA total of 689 ILI patients were recruited in this study with 355 in the oseltamivir therapy group and 334 in the supportive therapy group. Among the ILI patients, 388 patients were detected for IFV infection (364 IFV-A and 24 IFV-B) and divided into two groups with or without the oseltamivir therapy (302 vs. 86). There were no significant differences in the basic characteristics between the oseltamivir and supportive therapy groups in the ILI patients or in the IFV positive patients (all p < 0.05). After adjusting for the potential confounders, oseltamivir therapy reduced the times of clinic visits in the ILI and IFV positive patients (p = 0.043 and p = 0.011). No effectiveness with oseltamivir therapy was observed in the outcomes of hospitalization frequency, and the duration of fever and cough.ConclusionOseltamivir use may reduce the times of clinic visits. However, we did not observe the differences in the duration of fever, cough, and the frequency of hospitalization between oseltamivir therapy and supportive therapy.

Efficacy of oseltamivir in the treatment of patients infected with Covid-19

ObjectiveThe recent unprecedented pandemic caused by Sars-Cov-2 (the new coronavirus 2019), is threatening public health around the world. Although several studies have been performed, there is no identified treatment for Covid-19 patients. Here we assessed the efficacy of oseltamivir in combination therapy, by comparing two different therapeutic regimens in hospitalized patients, in improving outcomes and find better treatment for Covid-19 patients. MethodsThis is a single-center retrospective cohort study of 285 confirmed Covid-19 in patients at (XXX). Depending on the date of admission, the patients were divided into two groups; group 1 (oseltamivir group) from February 20, 2020 to March 15, 2020 received Oseltamivir with routine regimen and group 2 (control group) from March 20, 2020 to April 20, 2020 received routine regimen alone that included Azithromycin 500 mg/day and Hydroxychloroquine 200 mg/12 h.Endpoints including duration of hospitalization, requirement to admission to intensive care unit (ICU) and mechanical ventilation, outcome and mortality rate. ResultsA total of 285 patients were enrolled in the two months, 120 patients for group 1 and 165 for group 2. The median time from admission to discharge was significantly shorter in the oseltamivir group compared to the control group (4.9 vs 6.6 days, p < 0.001). Additionally, the mortality rate was found to be lower in the oseltamivir group than in the control group (1.7% vs 6,7%, p = 0.06) which was statistically significant by multivariate analysis (p = 0.03). The incidence of admission to the ICU (6.7% vs 11.5%, p = 0.1) and mechanical ventilation (2.5% vs 4.8%, p = 0.3) were also decreased in the oseltamivir group, but was not statistically significant. ConclusionsThis study showed that administration of oseltamivir was associated with shorter length of hospital stay and earlier recovery and discharge of hospital, and a lower mortality rate.

Inhaled Zanamivir vs Oral Oseltamivir to Prevent Influenza-related Hospitalization or Death: A Nationwide Population-based Quasi-experimental Study.

Meta-analyses of individual patient data from randomized, controlled trials show that early oseltamivir treatment for influenza cut the risk of pneumonia and hospitalization by 44% and 63%, respectively. However, data on the effectiveness of inhaled zanamivir in preventing hospitalization and death are lacking. This nationwide, population-based, cohort study included all outpatients treated with inhaled zanamivir or oral oseltamivir within 48 hours after a clinical diagnosis of influenza before and after the rollout of inhaled zanamivir as the first-line antiviral in Taiwan. The main outcome was influenza-related hospitalization or death within 14 days. Those who developed the outcome within 2 days were excluded from analyses. Propensity score stratification was used to control confounding from covariates. A total of 865 032 eligible influenza outpatients were included in the analysis. The risk of developing the main outcome (adjusted hazard ratio [aHR], 1.01; 95% confidence interval [CI], .96 to 1.06) did not differ between the inhaled zanamivir group (n = 595 897, 68.9%, the reference) and the oral oseltamivir group (n = 269 135, 31.1%). Prespecified analysis on high-risk subgroups further showed that inhaled zanamivir is not inferior to oral oseltamivir in either patients aged ≥65 years (aHR, 1.14; 95% CI: 1.05 to 1.25) or patients with chronic lung diseases (aHR, 1.23; 95% CI: 1.08 to 1.41). Inhaled zanamivir is not inferior to oral oseltamivir as outpatient treatment in preventing influenza-related hospitalization or death for patients whose conditions do not require hospitalization within 2 days.

Neuraminidase1 Inhibitor Protects Against Doxorubicin-Induced Cardiotoxicity via Suppressing Drp1-Dependent Mitophagy

Anthracyclines, such as doxorubicin (DOX), are among the effective chemotherapeutic drugs for various malignancies. However, their clinical use is limited by irreversible cardiotoxicity. This study sought to determine the role of neuraminidase 1 (NEU1) in DOX-induced cardiomyopathy and the potential cardio-protective effects of NEU1 inhibitor oseltamivir (OSE). Male Sprague–Dawley (SD) rats were randomized into three groups: control, DOX, and DOX + OSE. NEU1 was highly expressed in DOX-treated rat heart tissues compared with the control group, which was suppressed by OSE administration. Rats in the DOX + OSE group showed preserved cardiac function and were protected from DOX-induced cardiomyopathy. The beneficial effects of OSE were associated with the suppression of dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and mitophagy. In detail, the elevated NEU1 in cardiomyocytes triggered by DOX increased the expression of Drp1, which subsequently enhanced mitochondrial fission and PINK1/Parkin pathway-mediated mitophagy, leading to a maladaptive feedback circle towards myocardial apoptosis and cell death. OSE administration selectively inhibited the increased NEU1 in myocardial cells insulted by DOX, followed by reduction of Drp1 expression, inhibition of PINK1 stabilization on mitochondria, and Parkin translocation to mitochondria, thus alleviating excessive mitochondrial fission and mitophagy, alleviating subsequent development of cellular apoptotic process. This work identified NEU1 as a crucial inducer of DOX-induced cardiomyopathy by promoting Drp1-dependent mitochondrial fission and mitophagy, and NEU1 inhibitor showed new indications of cardio-protection against DOX cardiotoxicity.

Meta-analysis of randomized clinical trials of Riamilovir efficacy in etiotropic therapy of influenza

The aim of the study was to carry out a meta-analysis of randomized clinical trials in order to combine the results of clinical trials on Triazavirin® (Riamilovir) efficacy in etiotropic therapy of influenza.Materials and methods. The analysis was carried out in accordance with the PRISMA principles regarding the quality of information presentation on the results of systematic reviews and meta-analyzes of works assessing medical interventions. The study included 471 patients with a confirmed diagnosis of influenza (with laboratory confirmed presence of influenza virus antigens).Results. The conducted meta-analysis showed that the use of Triazavirin® (Riamilovir) has a statistically significant effect on the severity of clinical symptoms in patients with influenza, therefore Riamilovir can be used in the initial therapy of adult patients with influenza.Conclusion. Clinical studies have shown that the use of Triazavirin® (Riamilovir) is effective both in the initial and late stages of the disease, and therefore Riamilovir can be used in the treatment of adult patients with respiratory diseases of viral etiology, in particular, those diagnosed with influenza. The meta-analysis of the collected data showed that therapy with Triazavirin® (Riamilovir) has statistically significant advantages in various aspects both in comparison with the placebo group and with the Tamiflu® (Oseltamivir) group.

Clinical efficacy and safety of baloxavir marboxil in the treatment of influenza: A systematic review and meta-analysis of randomized controlled trials.

The aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza. PubMed, Embase, Web of Science, Google Scholar, Scopus, CINAHL, Cochrane databases and clinical registration were searched from inception until February 15 2021 for relevant randomized controlled trials (RCTs). Only phase 3 RCTs evaluating the usefulness of baloxavir in the treatment of influenza were included. Three RCTs enrolling 3771 patients (baloxavir group, n=1451; oseltamivir group, n=1288; placebo group, n=1032) were included. Compared with oseltamivir, baloxavir had an insignificantly shorter time to the alleviation of symptoms (mean difference [MD], -1.29h; 95% CI, -6.80 to 4.21; I2=0%). In contrast, baloxavir had a significantly shorter time to the alleviation of symptoms than placebo (MD, -26.32h; 95% CI, -33.78 to -18.86; I2=0%). Baloxavir was associated with a significant decline in influenza virus titers and viral RNA load compared to oseltamivir and placebo. Baloxavir was associated with a lower risk of any adverse events than oseltamivir (OR, 0.82; 95% CI, 0.69-0.98; I2=0%) and placebo (OR, 0.79; 95% CI, 0.66-0.96; I2=0%). The findings of this meta-analysis suggested that baloxavir is superior to placebo in the treatment of influenza in both clinical outcome and virological response. Moreover, baloxavir was found to have a better virological response than oseltamivir and to be as effective as oseltamivir clinically. Compared with oseltamivir and placebo, baloxavir appears to be a relatively safe anti-influenza agent.

Dexamethasone plus oseltamivir versus dexamethasone in treatment-naive primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial

Primary immune thrombocytopenia is an autoimmune bleeding disorder. Preclinical reports suggest that the sialidase inhibitor oseltamivir induces a platelet response in the treatment of immune thrombocytopenia. This study investigated the activity and safety of dexamethasone plus oseltamivir versus dexamethasone alone as initial treatment in adult patients with primary immune thrombocytopenia. This multicentre, randomised, open-label, parallel group, phase 2 trial was done in five tertiary medical hospitals in China. Eligible patients were aged 18 years or older with newly diagnosed, treatment-naive primary immune thrombocytopenia. Participants were randomly assigned (1:1), using block randomisation, to receive either dexamethasone (orally at 40 mg per day for 4 days) plus oseltamivir (orally at 75 mg twice a day for 10 days) or dexamethasone monotherapy (orally at 40 mg a day for 4 days). Patients who did not respond to treatment (platelet counts remained <30 × 109 cells per L or showed bleeding symptoms by day 10) were given an additional cycle of dexamethasone for 4 days in each group. Patients in the dexamethasone plus oseltamivir group who relapsed (platelet counts reduced again to <30 × 109 cells per L) after an initial response were allowed a supplemental course of oseltamivir (75 mg twice a day for 10 days). The coprimary endpoints were 14-day initial overall response and 6-month overall response. Complete response was defined as a platelet count at or above 100 × 109 cells per L and an absence of bleeding. Partial response was defined as a platelet count at or above 30 × 109 cells per L but less than 100 × 109 cells per L and at least a doubling of the baseline platelet count and an absence of bleeding. A response lasting for at least 6 months without any additional primary immune thrombocytopenia-specific intervention was defined as sustained response. All patients who were randomly assigned and received the allocated intervention were included in the modified intention-to-treat population analysis. This study has been completed and is registered with ClinicalTrials.gov, number NCT01965626. From Feb 1, 2016, to May 1, 2019, 120 patients were screened for eligibility, of whom 24 were ineligible and excluded, 96 were enrolled and randomly assigned to receive dexamethasone plus oseltamivir (n=47) or dexamethasone (n=49), and 90 were included in the modified intention-to-treat analysis. Six patients did not receive the allocated intervention. Patients in the dexamethasone plus oseltamivir group had a significantly higher initial response rate (37 [86%] of 43 patients) than did those in the dexamethasone group (31 [66%] of 47 patients; odds ratio [OR] 3·18; 95 CI% 1·13-9·23; p=0·030) at day 14. The 6-month sustained response rate in the dexamethasone plus oseltamivir group was also significantly higher than that in the dexamethasone group (23 [53%] vs 14 [30%]; OR 2·17; 95 CI% 1·16-6·13; p=0·032). During the median follow-up of 8 months (IQR 5-14), two of 90 patients discontinued treatment due to serious adverse events (grade 3); one (2%) patient with general oedema in the dexamethasone plus oseltamivir group and one (2%) patient with fever in the dexamethasone group. The most frequently observed adverse events of any grade were fatigue (five [12%] of 43 in the dexamethasone plus oseltamivir group vs eight [17%] of 47 in the dexamethasone group), gastrointestinal reactions (eight [19%] vs three [6%]), insomnia (seven [16%] vs four [9%]), and anxiety (five [12%] vs three [6%]). There were no grade 4 or 5 adverse events and no treatment-related deaths. Dexamethasone plus oseltamivir offers a readily available combination therapy in the management of newly diagnosed primary immune thrombocytopenia. The preliminary activity of this combination warrants further investigation. Multiple cycles of oseltamivir, as a modification of current first-line treatment, might be more effective in maintaining the platelet response. National Natural Science Foundation of China.

Rate of use and effectiveness of oseltamivir in the treatment of influenza illness in high-risk populations: A systematic review and meta-analysis.

BackgroundOseltamivir is recommended in the treatment of influenza illness in high‐risk populations, including those with chronic heart and lung diseases.ObjectivesWe conducted a systematic review and meta‐analysis to determine the rate of use and effectiveness of oseltamivir in these groups of patients.MethodsThe protocol for the systematic review was registered on PROSPERO (CRD42019125998). Medline, EMBASE, Cochrane CENTRAL, and CINAHL were searched for observational studies and randomized controlled trials published up to 16 February 2020. Quality appraisal of final studies was conducted using GRADE guidelines. Data were extracted using a predeveloped template. Main outcomes measured included the rate of use of oseltamivir for influenza‐like‐illness and its effectiveness in reducing disease severity in patients with cardiopulmonary diseases. Outcomes measured for effectiveness were influenza‐related complications (respiratory infections and asthma exacerbations), hospitalization rates, and time to freedom from illness. Risk of bias was assessed using Cochrane's Risk of Bias 2.0 tool for randomized trials and Cochrane's Risk of Bias in nonrandomized Studies of Interventions tool for nonrandomized trials. Where data were available, pooled analyses were conducted. Dichotomous variables were evaluated using the Mantel‐Hansel method. A random effect model was applied. Summary measures were reported as risk ratios where relevant.ResultsOur systematic review identified nine studies. Oseltamivir use ranged from 25% to 100%. When oseltamivir group was compared to placebo, rates of respiratory tract infections reduced by 28% (RR = 0.72, 95% CI = 0.59‐0.90), hospitalization reduced by 52% (RR = 0.48, 95% CI = 0.28‐0.80) and median time to illness alleviation decreased by 10.4 to 120 hours. There was no significant reduction in asthma exacerbation rates.ConclusionsOur systematic review suggests that the use of oseltamivir is beneficial in reducing disease severity, however, its use in high‐risk population remains suboptimal.

Применение противовирусного препарата, содержащего технологически обработанные антитела к интерферону-γ, CD4-рецептору и гистамину, для лечения гриппа у взрослых: результаты многоцентрового открытого рандомизированного сравнительного с осельтамивиром исследования

Objective. A multicenter open-label randomized controlled clinical trial was aimed to compare the efficacy of the study drug (SD) containing technologically processed affinity purified antibodies (high dilutions) to IFN-γ, CD4 receptor and histamine (Ergoferon) with oseltamivir, and evaluate the influence of SD on the antiviral immune response in adults with seasonal influenza. Patients and methods. 184 outpatients aged 18–70 with confirmed influenza of mild/moderate severity were included and randomized into 2 groups (in a 1:1 ratio). Patients received SD (Group 1, n = 92) or oseltamivir (Group 2, n = 92), according to the instructions for medical use for 5 days. As the primary endpoint, the percentage of patients with recovery/improvement was assessed (according to the data of the patient's diary on days 2–7 and according to the clinical examination on days 3 and 7). Additionally, the duration and severity of influenza symptoms, the percentage of patients with virus elimination (according to RT-PCR of nasopharyngeal samples), the percentage of patients with complications, the percentage of patients prescribed antipyretic drugs, the change in concentration of T cell (IL-2, IL-18, IFN-γ) and B cell antigen-specific (IL-4, IL-16) immune response regulators in serum, the leukocyte phenotypes on days 1, 3 and 7 were evaluated. Statistical analysis was performed using a “Non-Inferiority” design (or no less efficiency/safety). Intention-to-Treat (ITT) analysis data are presented. Results. According to patients’ self-assessment, 53.3% of patients in Group 1 recovered/improved on the 6th day in the morning and 65.2% – in the evening (vs. 53.3% and 57.6% in Group 2, respectively). There were 73.9% recovered/ improved patients on the 7th day in the morning (vs. 67.4% in Group 2). A generalized analysis showed that the treatment results in both groups were comparable (p &lt; 0.0001). According to objective medical examination, 79.3% of patients in the SD group and 74.0% of patients in the Оseltamivir group recovered/improved on the 7th day (p &lt; 0.0001). The antiviral efficacy of SD was not inferior to oseltamivir, which was confirmed by comparable periods of virus elimination, duration and severity of fever and other influenza symptoms. A moderate activating effect of SD on the immune system was evaluated. A significant, compared to oseltamivir, increase in the concentration of IL-2 and IL-4 on the 3rd day of treatment (p = 0.03 and p = 0.04 vs. the oseltamivir group), and IFN-γ on the 3rd and the 7th days (p = 0.012 and p &lt; 0.0001, respectively, vs. the oseltamivir group). No stimulating effect of SD on the growth and differentiation of immune cells was found. Conclusion. SD is effective and safe in the treatment of patients with influenza. The therapeutic and antiviral efficacy of SD is comparable to that of oseltamivir. The antiviral activity of SD affects the interferon system and the concentration of the cytokines IL-2 and IL-4, regulators of the T and B cell immune response. At the same time, there is no significant stimulation of interferon production with further development of hyporeactivity. Key words: influenza, oseltamivir, therapy, cytokines, Еrgoferon

Efficacy of oseltamivir compared with zanamivir in COPD patients with seasonal influenza virus infection: a randomized controlled trial.

Influenza viruses exacerbate chronic obstructive pulmonary disease (COPD) with considerable morbidity and mortality. Zanamivir and oseltamivir are effective in treating influenza. However, their efficacy in relieving influenza symptoms in COPD patients remains unknown, with the lack of controlled trials in this subject. Therefore, we conducted this randomized controlled trial to investigate the clinical efficacy of both interventions in this population. Patients were allocated to two groups (80 patients each): oseltamivir (OSELTA) and zanamivir (ZANA) groups. Oseltamivir (75 mg) was orally administered twice daily for 5 days, while zanamivir (10 mg) was inhaled twice daily for 5 days. Clinical parameters including body temperature, influenza symptoms (i.e., sore throat, cough, etc.), and serial blood tests were recorded on days 1, 3, and 7. We analyzed primary (changes in body temperature) and secondary outcomes (changes in non-specific symptoms) using the pre-protocol and intention-to-treat analyses. Differences between groups were assessed using t-test. Oseltamivir and zanamivir significantly reduced body temperature on the 3rd day after treatment; however, the number of patients who reported clinical improvement in influenza-like symptoms was significantly higher in the OSELTA group compared to the ZANA group on days 3 (85 vs 68.8%, P=0.015) and 7 (97.5 vs 83.8%, P=0.003). However, no significant changes in hematological (white blood cells and its subtypes) and inflammatory (C-reactive protein) parameters were noted (P>0.05). Our results suggested that oseltamivir and zanamivir are effective in reducing body temperature, while oseltamivir led to better clinical improvement regarding influenza-like symptoms in patients with COPD.

Comparison of Hospitalization Incidence in Influenza Outpatients Treated With Baloxavir Marboxil or Neuraminidase Inhibitors: A Health Insurance Claims Database Study

BackgroundBaloxavir marboxil (baloxavir) is a single-dose, oral antiinfluenza drug with a novel mechanism of action. We compared the incidence of hospitalization in patients treated with baloxavir vs neuraminidase inhibitors.MethodsIn this retrospective, observational, cohort study, we used real-world patient data extracted from a Japanese health insurance claims database. The enrollment period was 1 October 2018 to 17 April 2019. On day 1, eligible patients (N = 339 007) received baloxavir, oseltamivir, zanamivir, or laninamivir. Baseline characteristics were standardized using the inverse probability of treatment weighting method. The primary end point was the incidence of hospitalization (days 2–14). Secondary end points included antibacterial use, secondary pneumonia, and additional antiinfluenza drug use.ResultsCompared with the baloxavir group, the incidence of hospitalization was greater in the oseltamivir group (risk ratio [RR] and 95% confidence interval [CI], 1.41 [1.00–2.00]; risk difference [RD] and 95% CI, 0.06 [.01–.12]) and zanamivir group (RR, 1.85 [1.23–2.78]; RD, 0.11 [.02–.20]). Oseltamivir-treated patients were less likely to require antibacterials than baloxavir-treated patients (RR, 0.87 [.82–.91]). However, oseltamivir-treated patients were more likely to be hospitalized with antibacterials (RR, 1.70 [1.21–2.38]) or antibacterial injection (RR, 1.67 [1.17–2.38]) than baloxavir-treated patients (post hoc analysis). Compared with baloxavir-treated patients, additional antiinfluenza drug use was greater in oseltamivir-, zanamivir-, and laninamivir-treated patients (RR, 1.51 [1.05–2.18], 2.84 [2.04–3.96], and 1.68 [1.35–2.10], respectively).ConclusionsBaloxavir is an efficacious antiinfluenza treatment that may reduce hospitalization compared with oseltamivir and zanamivir.Clinical Trials RegistrationUniversity hospital Medical Information Network Clinical Trials Registry (UMIN000038159).

A retrospective comparison of drugs against COVID-19

Coronavirus disease 19 (COVID-19) has posed serious threats to the general population. To relieve the crisis, a comparison of drug effects against COVID-19 is instructive. Between January 27, 2020 and March 21, 2020, a total of 333 patients treated with arbidol, corticosteroids, hydroxychloroquine, lopinavir/ritonavir, or oseltamivir monotherapy, having definite outcomes and serological antibody detection results, were retrospectively analyzed. The hydroxychloroquine group had a significantly reduced duration of hospital stay than the arbidol and corticosteroids groups. The oseltamivir group had a significantly shorter length of hospital stay than the arbidol, corticosteroids, and lopinavir/ritonavir groups. The hydroxychloroquine group had a significantly higher IgM titer than the other four groups and exhibited significantly higher IgG levels than the arbidol, lopinavir/ritonavir, and oseltamivir groups. Our findings indicated that hydroxychloroquine might have the potential for efficient COVID-19 management, while oseltamivir should be prudently considered in combination therapy.